137382-32-2Relevant academic research and scientific papers
Metallation of pyridines and quinolines in the presence of a remote carboxylate group. New syntheses of heterocyclic quinones
Rebstock, Anne-Sophie,Mongin, Florence,Trecourt, Francois,Queguiner, Guy
, p. 291 - 295 (2004)
2-(3- and 2-Pyridylcarbonyl)benzoic acids (2,3), 2-(2-pyridylcarbonyl) thiophene-3-carboxylic acid (6), 2-(3-quinolylcarbonyl)benzoic acid (10), and most of the corresponding esters (compounds 1, 7 and 9) are readily synthesized and involved in a deprotonation-condensation sequence. Biologically active aza-anthraquinones such as benzo[g]isoquinoline-5,10-dione (2-azaanthraquinone, 4) and benzo[g]quinoline- 5,10-dione (1-azaanthraquinone, 5) are prepared using the strategy. Extension to other heterocyclic quinones such as thieno[3,2-g]quinoline-4,9-dione (8) and benzo[j]phenanthridine-7,12-dione (11) is also investigated.
The discovery of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 1
Bond, Silas,Draffan, Alistair G.,Fenner, Jennifer E.,Lambert, John,Lim, Chin Yu,Lin, Bo,Luttick, Angela,Mitchell, Jeffrey P.,Morton, Craig J.,Nearn, Roland H.,Sanford, Vanessa,Stanislawski, Pauline C.,Tucker, Simon P.
, p. 969 - 975 (2015/02/19)
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. Compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of A and B strains of RSV targeting the fusion glycoprotein. SAR was developed by systematic exploration of the phenyl (R1) and benzoyl (R2) groups. Furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted in active analogues with improved properties (aqueous solubility, protein binding and log D) and excellent rat pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17).
Approach to dual-acting platelet activating factor (PAF) receptor antagonist/thromboxane synthase inhibitor (TxSI) based on the link of PAF antagonists and TxSIs
Fujita, Masakazu,Seki, Taketsugu,Inada, Haruaki,Shimizu, Kazuhiro,Takahama, Akane,Sano, Tetsuro
, p. 341 - 344 (2007/10/03)
A series of compounds (22-36) which possess dual-acting PAF antagonist/TxSI have been generated by the approach of linking the known PAF antagonists and TxIs, such as Ridogrel (1).
Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
, p. 4052 - 4060 (2007/10/02)
A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
Novel Antiasthmatic Agents with Dual Activities of Thromboxane A2 Synthetase Inhibition and Bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones
Yamaguchi, Masahisa,Kamei, Kenshi,Koga, Takaki,Akima, Michitaka,Maruyama, Akinori,et al.
, p. 4061 - 4068 (2007/10/02)
A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A2 (TXA2) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated.While the length and the bulk of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity.Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b.These findings suggest that heteroaromatic nuclei at the 4-position of phthalazinones play a critical role in TXA2 synthetase inhibition.Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity.These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1(2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies.Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.
